Interaction of Concurrent Exercise Training and Milk thistle Extract on Hippocampi, NF-κB, and Serotonin of PTSD in Male Rats

Farah  Nameni; Fatemeh  Sorkheh; Fatemeh  Soltaniesmailzade

doi:10.18502/ehj.v12i1.21907

Farah Nameni Department of Exercise Physiology, VaP. C., Islamic Azad University, Varamin, Iran
Fatemeh Sorkheh Science and Research Branch, Islamic Azad University, Tehran, Iran
Fatemeh Soltaniesmailzade Science and Research Branch, Islamic Azad University, Tehran, Iran

DOI: https://doi.org/10.18502/ehj.v12i1.21907

Keywords: PTSD, Exercise Training, Milk Thistle Extract, Serotonin, NF-κB

Abstract

Introduction: Post-traumatic stress disorder (PTSD) is characterized by chronic neuroinflammation, impaired serotonergic signaling, and structural damage in both central and peripheral tissues, including the hippocampus and liver. Nuclear factor kappa B (NF-κB) plays a central role in stress-induced inflammatory responses. Exercise and phytotherapeutic agents such as milk thistle (Silybum marianum) have been suggested as potential non-pharmacological strategies for attenuating PTSD-related pathophysiology.

Methods: Fifty-five male Wistar rats were randomly assigned to five groups: healthy control, PTSD, PTSD with concurrent exercise training, PTSD with milk thistle extract, and PTSD with concurrent exercise training plus milk thistle extract. PTSD was induced using a multi-stage stress protocol. The concurrent exercise training program was conducted for 4 weeks, consisting of resistance training on even days and aerobic training on odd days. Resistance training was performed with progressively increasing loads from 50% to 80% of body weight, and aerobic training from 50% to 80% of VO₂max. Milk thistle extract was administered daily at a dose of 300 mg/kg. After the intervention, hippocampal and liver tissues were collected. NF-κB mRNA expression was measured using real-time PCR, and serotonin levels were measured by ELISA. Histopathological alterations were assessed by hematoxylin and eosin staining. Data were analyzed using ANOVA and Tukey statistical tests.

Results: PTSD induction significantly increased NF-κB mRNA expression and decreased serotonin levels in both hippocampal and liver tissues compared with healthy controls. Concurrent exercise training and milk thistle extract each significantly attenuated NF-κB overexpression and partially restored serotonin levels (p < 0.05). Histopathological analysis revealed severe neuronal degeneration in the hippocampus and marked structural damage in liver tissue in PTSD rats, whereas both interventions, particularly their combination, markedly improved tissue morphology.

Conclusion: Concurrent exercise training and milk thistle extract exert synergistic neuroprotective and hepatoprotective effects in a rat model of PTSD. These benefits appear to be mediated through suppression of NF-κB–dependent inflammatory pathways and restoration of serotonergic homeostasis